Platelet components associated with adverse reactions: predictive value of mitochondrial DNA relative to biological response modifiers
Résumé
Background: Biological Response Modifiers (BRMs), secreted by platelets during storage, play a role in Adverse Events (AEs) associated with transfusion. Moreover, mitochondrial DNA (mtDNA) levels in Platelet Components (PC) are associated with AEs. In this study we explore whether there is a correlation between pathogenic BRMs and mtDNA levels, and whether these markers can be considered predictors of transfusion pathology.
Study design and methods: We investigated a series of reported AEs after PC transfusion, combining clinical observations and mathematical modelling systems.
Results: mtDNA was consistently released during the first days of PC storage; however, mtDNA release was earlier in “pathogenic” than non-pathogenic PCs. PC supernatants with high levels of mtDNA along with sCD40L were significantly associated with occurrences of AEs. That mtDNA did not associate with the 14 BRM tested suggests the role of mtDNA in PC transfusion-linked inflammation is independent of that of BRMs, known to be associated with AEs. We present evidence that platelets generate distinct pathogenic secretion profiles of BRMs and mtDNA. The calculated Area Under the Curve (AUC) for mtDNA was significantly associated with AEs, although less stringently predictive than those of sCD40L or IL-13, standard predictors of AE. The established model predicts that distinct subtypes of AEs can be distinguished, dependent on mtDNA levels and PC storage length.
Conclusions: Further work should be considered to test the propensity of mtDNA in platelet concentrates to generate inflammation and cause an adverse event.